Flying Mammals and a New Jumping Gene

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Within our DNA are the remains of thousands, maybe millions, of genetic nomads. They once roamed free through the landscape of our genomes; now most are silenced and still, unable to move. These are the ‘jumping genes’, or ‘transposable elements’ to give them their proper name; curious stretches of mobile DNA.

Almost 50% of our DNA is made of these remnants. We see them in virtually all organisms, from bacteria, insects and fish all the way through to us humans. In mammals the only active jumping genes we’ve seen are a type called retro-transposons, which scatter copies of themselves throughout genomes. Now a new DNA sequence for a different type of jumping gene, the first active example of its kind ever to be seen in a mammal, has been spotted jumping around in the genome of the brown bat.

Transposable elements (TEs) come in two main groups, called the ‘retro-transposons’ and the ‘DNA transposons’. If our genomes were a book, DNA transposons would be like rogue paragraphs, able to leave one page for another, to cut and paste themselves elsewhere. The retro-transposons, on the other hand, are able to copy and paste themselves, replicating throughout the book. Some, presumably with the help of a virus, have even jumped into the ‘books’ of other species.

They’re not just interesting for their novelty value though. Retro-transposons, with their ability to copy themselves into other stretches of DNA, seemingly at random, may cause disease. One such element, called L1, has been spotted jumping into important genes, messing up how they usually work, leading to conditions like haemophilia and colon cancer. The same could be true of active DNA transposons.

Barbara McClintock won the Nobel prize for Physiology or Medicine for her the discovery of 'mobile genetic elements', TEs. She was also the first woman to win the prize unshared.

Barbara McClintock won the Nobel prize for Physiology or Medicine for her the discovery of ‘mobile genetic elements’, TEs. She was also the first woman to win the prize unshared.

Fortunately though, they can be thwarted. Random mutations in their sequence might be enough to prevent TEs from working, and most species have found ways of deactivating them. One example is by chemically labelling the DNA, such that the cells protein making machinery ignores them. Exactly how these defences arose is still not clear, though they are likely an important defence, not just against TEs, but also viruses that incorporate themselves into our DNA, like HIV, a retrovirus.

Now though we have the opportunity to see just how an active DNA transposon can affect a mammal and vice versa; the brown bat. The discovery was made by a research team, led by Professor Nancy Craig of the Howard Hughes Medical Institute, who were looking at an active DNA transposon of insects called piggyBac. A name given due to the way it can ‘piggyback’ on viruses to move between hosts.

The team set up a computer program to trawl through databases of different species DNA sequences, looking for stretches similar to piggyBac. A sequence from the brown bat popped out the other end as looking suspiciously similar, and active. They looked closer at the sequence; there were no obvious mutations that might stop it from working. This could be the first active DNA transposon ever found in a mammal. But was it really active?

To find out they delved deeper into the bats DNA sequence, and found around 30 similar copies of this sequence throughout its genome, suggesting that not only was it active, but that it arrived fairly recently. They decided the sequence needed a name, so, due to its similarity to the original piggyBac TE, they settled on the pun-tacular moniker ‘piggyBat’.

Next up they needed to see if it was truly still active. They extracted the DNA sequence and dropped it into human, bat and yeast cells. Sure enough, they saw evidence of it integrating itself inside them. This was a true, active, DNA transposon.

Scientists used to think that the last active DNA transposons to enter the genomes of mammals, and stay there, were about 40 million years ago. The evidence from the brown bat suggests there are much more recent events, less than a million years ago. As the researchers say in their paper, this discovery, for the first time, “opens an unprecedented opportunity to study the mechanism, regulation, and genomic consequences of a DNA transposon family caught in the midst of invading a mammalian host.”

TE's are responsible for the different colouring patterns on kernals of Indian Corn

TE’s are responsible for the different colouring patterns on kernels of Indian Corn

TEs are not all bad though. They may be a great force in evolution; depending on how, how well and where they are copied or inserted, they may cause things like duplications of genes. Gene duplications, over time, can result in all sorts of useful things like colour vision, or the development of snake venom (see Carl Zimmer’s fascinating post on the origin of snake venom here). Some of their remnants also appear to have been co-opted, or repurposed, for important bureaucratic and regulatory roles for other genes.

In the future TEs may even help us to treat diseases caused by faulty genes; a form of gene therapy. The idea is to insert a copy of the ‘normal’ gene into the TE DNA, let the TE do its thing, and fixing the new gene into the patient’s genome, curing the disease. This could do away with the need for using viruses to achieve the same end, which can be problematic, but there are still hurdles to overcome with TEs too. How to get the TE into the cells, how can we stop them inserting into and disrupting a normal gene, and how we can be sure it will stop ‘jumping’ once it’s there.

The one thing we can say for sure now though is that transposable elements are curious things and understanding how they affect us, and we them is an important part of unravelling our evolutionary development, and, with any luck they could be even be an important part of our medical future.

 

ResearchBlogging.org
Mitra, R., Li, X., Kapusta, A., Mayhew, D., Mitra, R., Feschotte, C., & Craig, N. (2012). Functional characterization of piggyBat from the bat Myotis lucifugus unveils an active mammalian DNA transposon Proceedings of the National Academy of Sciences, 110 (1), 234-239 DOI: 10.1073/pnas.1217548110

 

Image Credits:

Main image by Larry Meade, crudely altered by me

Indian corn by Alessandra Cimatti

Barbara McClintock from wikimedia